A Study of the Burden of Illness and Treatment Patterns in Teenagers and Adults With Hereditary Angioedema (BOISTERN)

A Retrospective Observational Chart Review Study Evaluating the Burden of Illness and Treatment Patterns in Hereditary Angioedema Type I and II

This study is about teenagers and adults with hereditary angioedema (HAE) type I and type II. In this study, the burden of illness means the impact of HAE in terms of long-term health outcomes and the financial cost.

The main aims of this study are as follows:

• to learn how often, how severe and where on the body HAE attacks occur.
• to describe how HAE prophylaxis and on-demand medicines are prescribed and used. (Prophylaxis medicines prevent a bleed from happening and on-demand medicines treat a bleed when it occurs.)

This study is about collecting data only; participants will not receive treatment as part of this study. Existing data available in the participant's medical records will be collected. Participants will be asked to complete an electronic questionnaire either on a website or by using an app on their mobile phone; data from this questionnaire will also be collected.

Participants do not need to visit their doctor in addition to their normal visits.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema

• Study Type: Observational
• Enrollment (Actual): 221

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medizinische Universitat Wien (Medical University of Vienna)
• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
• Bulgaria
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
• Canada
  • Hamilton, Canada, ON L8N 3Z5
    • McMaster University Medical Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, BCV5Y1K2
      • Vancouver Allergy Clinic
• Croatia
  • Zagreb, Croatia, 10000
    • Klinicki bolnicki centar Zagreb
  • Šibenik, Croatia, 22000
    • General Hospital Sibenik
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Praha, Czechia, 150 06
    • Fakultní nemocnice v Motole
• Estonia
  • Tallinn, Estonia, 10138
    • East Tallinn Central Hospital
• Germany
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt
• Greece
  • Athens, Greece, 115 27
    • Laiko General Hospital of Athens
  • Athens, Greece, 115 21
    • Navy Hospital of Athens
  • Larisa, Greece, 412 21
    • University General Hospital of Larissa
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem
• Ireland
  • Dublin, Ireland, D08 NHY1
    • St James's Hospital
• Israel
  • Ashkelon, Israel
    • Barzilai Medical Center
  • Haifa, Israel
    • Bnai Zion Medical Center
  • Ramat Gan, Israel
    • Sheba Medical Center - PPDS
  • Tel Aviv-Yafo, Israel
    • Tel Aviv Sourasky Medical Center PPDS
• Latvia
  • Rīga, Latvia, LV-1002
    • Pauls Stradins Clinical University Hospital
  • Rīga, Latvia, LV-1003
    • Centre of Investigation and Treatment of Allergic Diseases
• Lithuania
  • Kaunas, Lithuania, 50161
    • Hospital of Lithuanian University of Health Sciences Kauno Klinikos
  • Vilnius, Lithuania, 08410
    • Vilnius University Hospital Santaros Klinikos
• North Macedonia
  • Skopje, North Macedonia, 1000
    • Medical Faculty of Ss. Cyril and Methodius Univers
• Poland
  • Warszawa, Poland, 04-349
    • Wojskowy Instytut Medyczny
• Portugal
  • Coimbra, Portugal, 3004-561
    • Centro Hospitalar E Universitario de Coimbra EPE
  • Lisboa, Portugal, 1649-028
    • Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de São João, E.P.E.
• Romania
  • Sângeorgiu de Mures, Romania, 547530
    • MediQuest Clinical Research Center
• Serbia
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia - PPDS
• Slovakia
  • Martin, Slovakia, 036 01
    • Univerzitna Nemocnica Martin
• Slovenia
  • Golnik, Slovenia, 4204
    • Bolnisnica Golnik - Klinicni Oddelek za Pljucne Bolezni In Alergijo
• Spain
  • Barakaldo, Spain, 48903
    • Hospital Universitario Cruces
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants aged greater than or equal to (>=) 12 years with HAE type I or type II suffering from recurrent attacks will be enrolled in this study.

Description

Inclusion Criteria:

• Participant aged >= 12 years at the time of the last documented HAE attack in the eligibility period.
• Physician-confirmed diagnosis (or confirmation in medical records) of HAE type I or type II.
• Participant had at least one documented HAE attack during the eligibility period.
• Participant is not adequately or sub-optimally controlled according to treating physician.
• Participant (or parent/legal guardian) is willing and able to comply with the study requirements and provides informed consent or assent.

Exclusion Criteria:

• Participant enrolled in a therapeutic investigational drug or device trial during the observation period.
• Participant initiated long-term prophylaxis with Takhzyro® at any time since diagnosis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Participants with HAE; Participants' data will be collected retrospectively from electronic medical records using chart review of de-identified data on participant demographics, HAE medical history and information on diagnostics, treatments and disease course assessments that are routinely performed in accordance with current guidelines and/or local standard of care which are entered into an Electronic data capture (EDC) system over multiple data collection waves up to 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With HAE Attacks Occurrence During Study Period	HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Number of participants with HAE attacks occurrence (start and end date of each HAE attack) during study period will be reported.	Throughout the study period (up to 6 months)
Number of Participants Categorized Based on Characteristics of HAE Attacks During Study Period	HAE attack characteristics will be based on prodromal symptoms, severity and location, whether attack was life-threatening will be reported.	Throughout the study period (up to 6 months)
Time Interval Between HAE Attacks During Study Period	Time interval between HAE attacks during the study period will be reported.	Throughout the study period (up to 6 months)
Duration of Each HAE Attacks During Study Period	Duration of each HAE attacks during study period will be reported.	Throughout the study period (up to 6 months)
Number of Participants Based on Type of HAE Prophylactic Treatments	Number of participants based on type of HAE prophylactic treatment will be reported.	Throughout the study period (up to 6 months)
Number of Participants Based on Long-term or Short-term HAE Prophylactic Treatment	Number of participants based on long-term or short-term HAE prophylactic treatment will be reported.	Throughout the study period (up to 6 months)
Number of Participants Categorized Based on Reasons for HAE Prophylactic Treatment Initiation	Number of participants categorized based on reasons for HAE prophylactic treatment initiation will be reported.	Throughout the study period (up to 6 months)
Duration of HAE Prophylactic Treatment	Duration of HAE prophylactic treatment includes treatment start and end dates will be reported.	Throughout the study period (up to 6 months)
Number of Participants Categorized Based on Dose and Route of Administration for HAE Prophylactic Treatment	Number of participants categorized based on dose and route of administration for HAE prophylactic treatment will be reported.	Throughout the study period (up to 6 months)
Number of Participants Categorized Based on Reasons for HAE Prophylactic Treatment Discontinuation	Number of participants categorized based on reasons for HAE prophylactic treatment discontinuation will be reported.	Throughout the study period (up to 6 months)
Number of Participants Based on Type of HAE On-demand Treatment	Number of participants based on type of HAE on-demand treatment will be reported.	Throughout the study period (up to 6 months)
Duration of HAE On-demand Treatment	Duration of HAE on-demand treatment includes treatment start and end dates will be reported.	Throughout the study period (up to 6 months)
Number of Participants Categorized Based on Dose and Route of Administration for HAE On-demand Treatment	Number of participants categorized based on dose, route of administration and setting of administration for HAE on-demand treatment will be reported.	Throughout the study period (up to 6 months)
Number of Participants Associated Between Prescriptions Patterns and HAE Attacks	Number of participants with association between prescriptions patterns and HAE attacks related to frequency or severity. Generalized linear models (GLM) will be used to evaluate the association of outcomes of interest with relevant covariates between prescription pattern, HAE attacks, frequency and severity of HAE attacks will be reported.	Throughout the study period (up to 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healthcare Resource Utilization (HRU): Number of Visits to Healthcare Professionals (HCP)	HRU is measured by the number of visits to HCP will be reported.	Throughout the study period (up to 6 months)
HRU: Number of Participants With Emergency Room/Emergency Departments (ER/ED) Visits due to HAE Attacks	Number of participants with ER/ED visits due to HAE attacks will be reported.	Throughout the study period (up to 6 months)
HRU: Number of Participants With Hospitalizations due to HAE Attacks	Number of participants with hospitalizations due to HAE attacks will be reported.	Throughout the study period (up to 6 months)
Health-related Quality of Life (HRQoL): Angioedema Quality of Life (AE-QoL) Questionnaire	The AE-QoL was developed to measure HRQoL in participants with recurrent angioedema. It is a self-administered patient-reported outcome instrument with a recall period of four weeks. There are 17 items across four domains: functioning (four items), fatigue/mood (five items), fears/shame (six items), and food (two items). Responses use a 5-point Likert scale ranging from 1 (Never) to 5 (Very Often). Global scores range from 0 to 100 and scores by domains range from 0 to 100. An overall score is calculated and a higher score indicates lower quality of life.	Throughout the study period (up to 6 months)
HRQoL: EuroQoL Group 5-Dimension 5-Level (EQ-5D-5L) Questionnaire	The EQ-5D-5L descriptive system assesses health in five dimensions (Mobility, Self-Care, Usual Activities, Pain / Discomfort, Anxiety / Depression), each of which has five levels of response (no problems, slight problems, moderate problems, severe problems, extreme problems/unable to). This part of the EQ-5D questionnaire provides a descriptive profile that can be used to generate a health state profile. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The second part of the questionnaire consists of a visual analogue scale (VAS) on which the participant rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health).	Throughout the study period (up to 6 months)
HRQoL: EuroQoL-five Dimensions, Youth Version (EQ-5D-Y)	The EQ-5D-Y is composed of two sections. The first section contains one question for each of the five dimensions: mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy. Participants select from three response levels (no problems, some problems, a lot of problems) for each dimension. A health state profile score can be calculated from the responses on these five questions. The second section includes the same visual analogue scale as the EQ-5D-5L. The scale is scored from 0-100. The reference to a high score indicates a better outcome of quality of life.	Throughout the study period (up to 6 months)
Number of Participants With HAE Attacks Occurrence in Relevant Subgroups	HAE attack is defined as the symptoms or signs consistent with an attack in at least 1 of the following locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE). Number of participants with HAE attacks occurrence (start and end date of each HAE attack) in relevant subgroups will be reported.	Throughout the study period (up to 6 months)
Number of Participants Categorized Based on Characteristics of HAE Attacks in Relevant Subgroups	HAE attack characteristics will be based on prodromal symptoms, severity and location, whether attack was life-threatening in relevant subgroups will be reported. Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE).	Throughout the study period (up to 6 months)
Time Interval Between HAE Attacks in Relevant Subgroups	Time interval between HAE attacks in relevant subgroups will be reported. Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE).	Throughout the study period (up to 6 months)
Duration of Each HAE Attacks in Relevant Subgroups	Duration of each HAE attacks in relevant subgroups will be reported. Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE).	Throughout the study period (up to 6 months)
HAE Attacks Prescription Pattern in Relevant Subgroups	Prescription pattern of HAE attacks medication by drug class in relevant participant subgroups during study period. Relevant subgroups is defined by disease characteristics (e.g., number of attacks) and treatment patterns (type of treatments for HAE).	Throughout the study period (up to 6 months)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Actual): January 13, 2023
• Study Completion (Actual): January 13, 2023

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: July 5, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Actual): June 26, 2023
• Last Update Submitted That Met QC Criteria: June 23, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: TAK-743-4009; MACS-2020-080401 (Other Identifier: Sponsor)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No